A variety of sustained release formulations for delivery of water-soluble products such as drugs, proteins and nucleic acids are known in the art. Among these are techniques for the preparation of polymer microspheres, via spray drying, spray congealing, coacervation, or solvent evaporation, which provide for the sustained release of encapsulated bioactive materials. Many encapsulation techniques utilize polymers dissolved in an organic medium and then emulsified in water, a so-called oil-in-water process (O/W), for encapsulating water-soluble material. Water-soluble products partition into an aqueous medium, however, and in general, such methods result in low encapsulation efficiency. Similarly, encapsulation via water-in-oil-in-water or oil-in-oil (O/O) emulsion processes suffer limitations including the use of different organic solvents, first to solubilize the polymer, and then to wash the polymer microspheres free of the oil in which they are formed, and subsequent removal of the solvents.
A major complicating factor in achieving high encapsulation efficiency of peptides, nucleic acids and some drugs is their water solubility. Solubility of, for example, peptides is considerably reduced, however, when the peptide is present as a free base, due to intermolecular interactions. One method of enhancing the encapsulation efficiency of the peptides in an O/W process is by using a peptide as a free base adsorbed onto a bioresorbable inorganic matrix, however, pH conditions must be carefully maintained, or the solubilization of the peptide may occur, leading to poor encapsulation efficiency. In addition, such encapsulation does not provide a controlled release mechanism.
Thus there remains a need for high loading, controlled release mechanisms in microencapsulated water-soluble products.